ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Jose Gatell presented data from an elegant study focused on virologically suppressed individuals with high cardiovascular risk.They were aged 50 years or older and had Framingham cardiovascular risk greater than or equal to 10 percent.They switched from PI/r-based to dolutegravir-based regimen and showed non-inferior virologic efficacy with improvements in lipid profile at wk48.Other outcomes from this ongoing trial are awaited.

Laura Ciaffi showed data from a switching study.After viral suppression with second-line PI/r+NRTIs, maintenance with PI/r+lamivudine showed virologic efficacy at wk 96 despite the presence of the M184V mutation.This study was conducted in Africa.This is an example of the increasing number of dual therapy studies presented at IAS this year.

Kathleen Squires presented data comparing a fixed dose combination of doravirine/lamivudine/TDF to efavirenz/emtricitabine/TDF in treatment-naïve adults with HIV-1 infection.It showed non-inferiority at week 48 regardless of the baseline HIV RNA.Doravirine also showed superior neuropsychiatric and lipid profile in these results of the Phase 3 DRIVE-AHEAD study.A useful extension of this study would be a co-formulation of doravirine with FTC/TAF to reduce the renal and bone effects well known with TDF.

Finally, Trevor Crowell presented data from a study using one of the newer approaches to HIV treatment, broadly neutralising antibodies.In virologically suppressed individuals who initiated ART during acute HIV infection, VRC01 was well-tolerated.However, VRC01 monotherapy was insufficient to maintain viral suppression.This is an early setback but this will benefit future research in this area.Broadly neutralising antibodies are being used in a growing area of research to assess alternative approaches to therapy besides daily oral therapy.On a more reflective note, another theme from the conference this year was to start treatment as soon as possible to reduce the potential viral reservoir which we know is concentrated in lymphoid tissues.This is likely to enhance prospects of cure or functional cure when future therapies become available.

Presented as part of the mixed bag "Co-chair's Choice" session this study aimed to assess dolutegravir (DTG) in pregnancy. There are many benefits to DTG as treatment, highly effective, well tolerated, once daily with high barriers to resistance.However, despite being a drug with many desirable qualities, the lack of data in pregnancy have resulted in DTG not being recommended in pregnancy by the WHO.This study addresses some of the research shortfalls and compared pregnancy outcomes from patients who used EFV/TDF/FTC between August 2014 and August 2016 and those who used DTG/TDF/FTC from November 2016 to April 2017

Much of the groundwork for this study was laid out by the Tsempano study, which demonstrated that EFV/TDF/FTC was associated with lower rates of any adverse birth outcomes as well as lower rates of severe adverse birth outcomes compared with other ART regimens (NVP/TDF/FTC, NVP/ZDV/3TC, LPV/r/TDF/FTC, LPV/r/ZDV/3TC).A similar framework was adopted for the comparison of DTG/TDF/FTC with EFV/TDF/FTC in women who commence ART pregnancy.

Maternal demographics were well matched in both groups for age, employment, parity, gestational age at presentation, previous pregnancy losses and smoking and alcohol consumption.They were also well matched with regards to the gestational age at which ART was commenced as well as their CD4 counts.

Outcomes were startlingly similar as listed below:

Total and severe adverse birth outcomes 34% in the DTG/TDF/FTC group, with 11% being a severe adverse birth outcome.

Total and severe adverse birth outcomes 35% in the EFV/TDF/FTC group, with 11% being a severe adverse birth outcome.

Birth at less than 37 weeks gestation 18% and less than 32 weeks gestation 4% in the DTG/TDF/FTC group

Birth at less than 37 weeks gestation 19% and less than 32 weeks gestation 4% in the EFV/TDF/FTC group

19% small for gestational age and 6% very small for gestational age in the DTG/TDF/FTC group

19% small for gestational age and 7% very small for gestational age in the EFV/TDF/FTC group

2.1% stillbirth in the DTG/TDF/FTC group

2.3% stillbirth in the EFV/TDF/FTC group

1 major congenital abnormality in the form of skeletal dysplasia in the EFV/TDF/FTC group

This preliminary data suggests that DTG may well be considered safe in pregnancy at some point but further research is needed in the following areas:

B/F/TAF was safe, well tolerated and non-inferior to DTG/F/TAF in treatment naïve adults. Discontinuations due to adverse events were uncommon in both arms . There was no evidence of treatment-emergent resistance to study medication. Interestingly there was less of a decrease in the e GFR observed in the B/F/TAF participants. No difference observed in lipids.

This session was about emerging therapies for HIV and new approaches to specific patient populations.The topics covered in this session included immunodeficiency at the time of ART initiation and the use of various ART combinations in different settings such as advanced immunodeficiency, second-line ART resistance and the use of novel 2 and 3 drugs combinations in ART-naive individuals.

The first speaker, Nanina Anderegg showed that median CD4 count at ART initiation was <350 cells/µL, with >25% of individuals at CD4 count <200 cells/µL, in low, middle and high income countries in 2015.They analysed data from the International epidemiology Databases to Evaluate AIDS (IeDEA) in sub-Saharan Africa, Latin America, Asia-Pacific and North America regions and from the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). They included all HIV-positive adults (≥16 years) initiating cART between 2002 and 2015.This demonstrated that a substantial number of individuals still initiated ART at advanced immunodeficiency. Additional efforts and resources are needed to improve testing coverage, linkage to care, and ART initiation globally.There was a general trend to start ART at higher CD4 counts in the later years of the study though, which is encouraging.

Lelièvre found that the addition of maraviroc (MVC) to standard ART in advanced HIV infection had no impact on the risk of occurrence of infections, serious events and mortality, virological control or CD4 count recovery.However, post hoc analysis showed a trend for a beneficial effect of the addition of MVC in the first 24 weeks in CD4 count recovery that disappeared thereafter.Therefore miraviroc may be of some benefit in immune system reconstitution in early stages of therapy.

Moh reported that in individuals failing second-line PI-based regimens, a phase of intense adherence reinforcement with HIV-RNA monitoring may help determine whether switching to a third-line regimen is required.

Joel Gallant showed that bictegravir/emtricitabine/tenofovir alafenamide was non-inferior to dolutegravir/abacavir/lamivudine in terms of virologic efficacy and was well tolerated.This was in treatment naïve subjects and their data extends to 48 weeks.The single-tablet formulation bictegravir/emtricitabine/tenofovir alafenamide is potentially suited to the setting of same day/rapid ART initiation as it can be safe to start pending hepatitis B screening results, has high virological efficacy and favourable safety profile.This study is ongoing.

In other treatment-naïve individuals, simplified combinations such as ritonavir-boosted darunavir/lamivudine was shown to be non-inferior to ritonavir-boosted darunavir/lamividuine/tenofovir in achieving HIV-RNA <400 copies/mL at week 24 as presented by Pedro Cahn.Dolutegravir/lamivudine also demonstrated potent virologic efficacy at week 24 in individuals with entry HIV-RNA <500,000 copies/mL thanks to data presented by Babafemi Taiwo.Early data suggest that simplified regimens consisting of ART with a high resistance barrier and lamivudine may be non-inferior in virologic control in treatment-naïve individuals. Data with larger sample sizes and longer follow-up are needed to confirm these findings.

At one particular session of the 2nd Asia Pacific AIDS & Co-infections Conference (APACC) that took place from 1 to 3 June 2017 in Hong Kong, Dr. Dan Kuritzkes (Harvard Medical School, USA) started his presentation by asking the question, 'Why do we need new drugs?'

The answers being:

Side effects of current therapies.

Long term toxicities of current ART.

Resistance issues.

Need for less frequent dosing.

He then went on to discuss new medications in development/trials.

DORAVIRINE (NNRTI) — This drug is active against HIV carrying the common NNRTI resistance mutations, it has low potential for drug-drug interactions and has the same efficacy as Effavirenz.

Dan went on to discuss the pros and cons of different types of treatment delivery such as injectables.

ProsCons

Monthly dosing The injection itself may put clients off

More convenient Long term tolerability

Less internal stigma Long half life

Better adherance Cannot be self-administered

An interesting snippet was that TRUVADA is being researched as an injectable. This ties in with Dr. Zhang's presentation who stated that TRUVADA as a single tablet wasnt available in China and called for a new way to deliver this medication especially in the setting of PrEP. Dan mentioned a few other drugs in development but didnt elaborate much on them. These being:

IBALIZUMAB, FOSTEMSAVIR and PRO140.

The summary of Dr. Kuritzkes' session is:

There are new drugs in several classes undergoing clinical trials.

Different delivery systems are being researched.

Novel viral and cellular targets are being explored rather than the traditional classes.